Jamahiriya Medical JournalShort Communication                               Published by the Libyan Board of Medical Speci...
Alarabi R et al                                               The study of ER (Oestrogen Receptor), PR (Progesterone Recep...
Alarabi R et al                                                                                                           ...
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  1. 1. Jamahiriya Medical JournalShort Communication Published by the Libyan Board of Medical Specialities The study of ER (Oestrogen Receptor), PR (Progesterone Receptor) and HER-2/neu Status in Patients with Breast Cancer Mohd Shafi Moona, Ramah Al-Rameh Alarabi, Arshad Hussain, Mahmood Ahmad and Itrat Mehdi Department of Medical Oncology, African Oncology Institute Sabratha, LibyaABSTRACT:Introduction: Breast cancer is a major health issue in Oncology practice in Libya, and is the most frequent female cancer inall age groups in Libya as it is globally. The optimal management of breast cancer cannot be accomplished without thedetermination of ER, PR, and HER2. These receptor/ determinations have diagnostic, therapeutic and prognosticimplications. Aim of the Study: The aim of this study was to determine and analyze retrospectively the hormone receptorsER and PR status, and HER2 status in patients with breast cancer treated at the African Oncology Institute, Sabratha, Libyabetween January 2008 to December 2008 (12 months). The receptor positivity was further analysed with respect to clinicalstage at presentation. Patients and methods: This was a hospital based retrospective study of patients with breast cancerenrolled at the African Oncology Institute, Sabratha, Libya from January 2008 to December 2008 (8 months). The data ofthese patients was retrieved from their original files where the reports of ER, PR were available by immunocytochemistry.The HER2 results were seen as conclusive by immunocytochemistry or supplemented by FISH, wherever indicated. Theresults were tabulated, analysed, and presented as tables or in descriptive form. Results: A total of 100 cases with completedata were retrieved. The majority were Carcinoma staging (CS) III (40%), while CS I (3%) were the least encountered.Triple positives were 15% and triple negatives were also 15%. HER2 positives were 30%. 22% had an unknown status.Discussion: ER, PR, and HER2 receptor determination is vital to standard and state of art breast cancer management. Thereare issues of availability and quality control, particularly in the developing World. The interaction between the three isanother arena which needs further exploration.KEYWORDS:-ER, PR, HER2/neu, AOI, Sabratha, Breast cancer, IHC, FISH. (JMJ 2010,Vol.10, No.2 , 141-143).INTRODUCTION: Hormone receptors are distributed in the human bodyBreast cancer is the most common cancer in women in all mainly in the female reproductive organs but also in non-age groups anywhere in the world. The life-time risk of reproductive organs as well.developing breast cancer is about one in twelve. There The ER and PR levels vary in different tissues. Theirare many hormonal genetic risk factors such as age of levels are also influenced by factors such as age, obesity,menarche < 12 , multiparity, age of first childbirth > 30 and existence of cancer. Down regulation and upgradingyears and a family history of first degree relatives with of receptors are also very well established phenomena inabout 4 to 6 times risk more than other women. Hormone human physiology. Breast cancers that are ER, PRreceptors and HER2 status plays an important role in the receptor-negative are associated with the worst outcomesdiagnosis, management and prognosis of breast cancer. and require aggressive treatment right from the time of diagnosis (1-3). Studies done at the Mayo Clinic found that survival is shortened and had the worst overallReceived 20-09-2009 ; Accepted 08-01-2010. outcome, when ER; PR negative breast cancer spread toCorrespondence and reprint request: the brain, because of this, these patients should be treatedItrat Mehdi aggressively after an initial diagnosis, to minimize suchDepartment of Medical Oncology, African Oncology Institute metastasis. The cancers include so called triple negativeSabratha, LibyaE-mail: Itrat -Mehdi@yahoo.com tumours. (cancer that does not exhibit HER2 growth factors or oestrogen (ER), progesterone receptors (PR)) and as well as HER2 positive cancers that are alsoJ M J Vo1. 10 No.2 (Summer) 2010 www.jmj.org.ly Page 141
  2. 2. Alarabi R et al The study of ER (Oestrogen Receptor), PR (Progesterone Receptor)ER/PR negative. Targeted therapies are available for regimens.cancers that are ER/PR+ve or HER2+ve before they The assessment of ER, PR and HER2 is made routinely inmetastasize to the brain. Trastuzumab (Herceptin) which every breast cancer patient to have information aboutis used to treat HER2+ve cancer, is too large to breach the prognosis and to select patients who are candidates forblood brain barrier. The patients who have triple negative hormonal and anti-HER2 therapy. A proportion of(HER2- , ER-, and PR -ve) breast cancers do not benefit patients show discordances in hormonal receptor andfrom targeted therapies. More aggressive therapy may be HER2 expression between the primary tumour and theneeded because patients with ER/PR -ve disease tend to paired recurrent/metastatic lesions. As these discordantdevelop brain metastasis even if the cancer has not results make changes in treatment decision, a biopsy ofspread anywhere else, and this metastasis develops the metastatic lesion should be recommended insooner and survival is shorter compared to breast cancer metastatic breast cancer patients when feasible (10).that is ER/PR +ve (4).Breast cancer patients with tumours that are receptor PATIENTS AND METHODS:positive have a lower risk of mortality after their This is a retrospective study, which was carried out over adiagnosis compared to women with negative hormone period of twelve months from January 2008 to Decemberreceptors. For patients who are hormone receptor- 2008 at the African Oncology Institute, Sabratha, Libya.positive, it may be necessary to have a long-term The data was retrieved from archive files of the femaletreatment because the risk is retained. If the patient has patients diagnosed with breast Cancer. ER, PR receptoralready received 5 years of tamoxifen and is and HER2 status were analyzed and proper TNM stagingpostmenopausal at the end of treatment, she could benefit was done. The cases having a reliable determination offrom another endocrine manipulation with an aromitase ER, PR, and HER2 by immune cytochemistry wereinhibitor because it continues to decrease risk of included, supplemented by FISH in cases of HER2metastatic disease of contralateral breast (5). If the wherever indicated. Clinical stage was correlated todisease has nodal involvement, the overall survival is receptor status as well. The data was tabulated andimproved further with extended treatment. Women with analyzed to see ER, PR, HER2 positivity or negativityhormone receptor negative breast cancer who remain either alone or in correlation to each other.disease free for five years are less likely to relapse thanare those with hormone receptor positive disease, and RESULTS:therefore this group might be candidates for less frequent The total number of patients was 100 patients with theexamination (6). following stage distribution: stage I - 3%, stage II - 27%,Human epidermal growth factor receptor (EGFR2) stage III - 40%, and stage IV - 29%.(Fig.1).became established not only as a prognostic marker but The receptor (ER, PR, and HER2 status) distribution was:also as a predictive factor for early-stage and metastatic ER, PR, HER2 +ve (15%); ER, PR +ve (25%); HER2breast cancer. The discovery of the role of HER2 in breast +ve (9%); ER +ve (3%); PR +ve (5%); ER, HER2 +vecancer was one of the landmarks in breast cancer research 4%; PR, HER2 +ve (2%); ER, PR, HER2 -ve 15% andin the last 2 decades. HER2 is over expressed in 20-30% unknown status 22%.(Fig.2)of breast cancers. Tumour cells over expressingHER2/neu may have up to 2 million copies of thereceptor on their surface compared to with 20000- 50000copies on normal breast epithelial cells. HER2 is used as apredictive marker for therapy with trastuzumab, thehumanized monoclonal antibody, or lapatinib (atyrosine 45%kinase inhibitor). HER2+ve breast cancers are more 40%aggressive than HER2-ve tumours. Patients with HER2+ 35%disease have a significantly shorter disease free survival stage 1 30%and overall survival, regardless of lymph node st age 11 25%involvement and other prognostic factors(7). The stage 111 20%association between HER2 status and responsiveness to stage 1Vadjuvant anthracyclines may be related to the tumour 15% Unknow nlevel of topoisomerase 11 alpha, the molecular target of 10%anthracyclines (8,9) . In fact, the gene encoding 5%topoisomerase 11 alpha is located adjacent to the HER2 0%on chromosome 17. Anthracyclines have no effect on %patients with breast cancer that is HER2 - ve, and so thesepatients could be spared unnecessary toxic effects fromthis class of agents. Anthracycline-based regimens havebeen shown to be superior to non-anthracycline-based Figure 1 Patients Distribution According to N T Mregimens for disease-free and overall survival in women Staging.with early breast cancer. Women with over expressed oramplified HER2 may respond better to anthracyclinePage 142 www.jmj.org.ly J M J Vo1. 10 No.2 (Summer) 2010
  3. 3. Alarabi R et al The study of ER (Oestrogen Receptor), PR (Progesterone Receptor) REFERENCES: 1- Adami HO; Graffman S; Lindgren A; Sallstrom 50 47 47 J.Prognostic implication of estrogen receptor content in 45 40 breast cancer. Breast Cancer Res Treat 1985;5(3) : 293- 35 30 300. 30 25 25 22 2-Parl FF, Schmidt BP, DuPont WD, Wagner RK: 20 15 15 Prognostic significance of estrogen receptor status in 15 10 9 breast cancer in relation to tumour stage, axillary node 5 5 3 4 2 metastasis, and histopathologic grading. Cancer 1984; 0 54:2237-2242. + - n ER PR ER + + + + + + R w ER ER ER PR ER ER R no E ll H 3-Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. ll ll ,P H ra ra ,H ,H ,H nk H ra ER R, ve ve U R ER PR ve P O O ,P O R, Breast cancer subtypes on ER/PR and Her2 expression:ER E Comparison of clinicopathologic features and survival. Department of Haematology/Oncology, Marshfield Clinic Weston Centre, Weston, Wisconsin 54401, USA.Figure 2 The Receptor (ER, PR, and HER2 Status) 4-Stephanie Hines , Laura Vallow. Survival shortenedDistribution. when ER/PR negative breast cancer spreads to the brain. Mayo Clinic; 2007;December 17.DISCUSSION: 5-Goss PE, Ingle JN, Martino S, et al.Randomized trial ofOestrogen receptor (ER), Progesterone receptor (PR), or letrozole following tamoxifen as extended adjuvantHER2 have practical and vital implications in the therapy in receptor-positive breast cancer: updateddiagnosis, management, prognostication, and treatment findings from NCIC CTG MA-17. J Natl Cancer Instoutcome determination in breast cancer. Positivity 2005; 97; 1262.confers a better prognosis, and may indicate the 6-Crowe JP Jr, Gordon NH, Hubay CA, Shenk RR,justifiable use of a hormonal or targeted treatment Zollinger RM, Brumberg DJ, McGuire WL, Shuck JM:modality. Triple negative disease has the worst outcome. Estrogen receptor determination and long term survivalThis receptor determination may often be used to of patients with carcinoma of the breast. Surg Gynecoldetermine the primary disease in cases of metastatic Obstet 1991; 173:273-278.breast cancer presenting as MUO (metastasis of 7-Tandon AK; Clark GM; Chamness GC; Ullrich A;undetermined origin). McGuire WL. Her-2/neu oncogene protein andThe availability, cost, and quality assurance of these prognosis in breast cancer. J Clin Oncol 1989; 7(8):sophisticated receptor analyses are often a luxury and 1120-8.reporting is suboptimal especially in the developing 8-Piccart-Gebhart MJ, Procter M, Leyland -Jones B, etworld. This on one hand leads to misdiagnosis and in- al. Trastuzumab after adjuvant chemotherapy in HER2-appropriate treatment, while changing the balance of positive breast cancer. N Engl J Med 2005; 353:1659.cost- effective management on the other. The concept of 9-Perez EA, Romond EH, Suman VJ, et al.Updatedevidence- based medicine is not that easy to practise, and results of the combined analysis of NCCTG N9831.financial burdens on health care can often be And NSABP B-31 adjuvant chemotherapy with/withoutoverwhelming. trastuzumab in patients with HER2-positive breastAs it is apparent from the data presented, the receptor cancer. Proc Am Soc Clin Oncol. 2007;25:6s.status is still not available to a substantial number of (Abstract 512).patients due to lack of availability, cost, or unawareness. 10-Chen Shin-Cheh, Chang Hsien-Kun, Lin Yung-The results were in line with the results available in Chang, et al. High Pathologic complete Response ininternational literature. The clinical stage at presentation HER 2-positive Locally Advanced Breast Cancer afterhowever is late comparatively, which have a negative Primary Systemic. Chemotherapy with Weeklyeffect on the final outcome. Docetaxel and Epirubicin. Japanese Journal of ClinicalTriple receptor positivity or otherwise has a significant Oncology Advance Access February 12, 2008;vital impact on treatment, treatment options, treatment doi:10.1093/jjco/hym172: 2-7outcome, prognostication, prediction and survival. Thedata need to be analyzed in depth with different subgrouppopulations, and needs to be compared with internationaldata. It would be interesting to study the relationship ofreceptor status with reference to age, bodyweight, andserum hormone levels of the patients. The analysis canalso be done retrospectively to find the appropriatenessof treatment given and subsequent outcomes.J M J Vo1. 10 No.2 (Summer) 2010 www.jmj.org.ly Page 143